Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Resul...

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Published inJournal of the American Heart Association Vol. 9; no. 12; p. e017144
Main Authors Ramireddy, Archana, Chugh, Harpriya, Reinier, Kyndaron, Ebinger, Joseph, Park, Eunice, Thompson, Michael, Cingolani, Eugenio, Cheng, Susan, Marban, Eduardo, Albert, Christine M, Chugh, Sumeet S
Format Journal Article
LanguageEnglish
Published England John Wiley and Sons Inc 16.06.2020
Wiley
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Summary:Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms ( =0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus -0.2±28 ms in women; =0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; =0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.
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For Sources of Funding and Disclosures, see page 7.
Preprint posted on MedRxiv, April 25, 2020. doi: https://doi.org/10.1101/2020.04.22.20075671.
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.120.017144